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A novel self-curing active cold patch asphalt mixture: Performance evaluation and mechanism analysis
Get PDFCold patch asphalt mixtures (CPAMs) are increasingly favored for pothole repairs in asphalt pavements due to their environmental benefits and ease of construction. However, their low strength and durability have hindered broader application, necessitating the development of CPAMs with enhanced engineering performance. To address these challenges, this study proposes a novel self-curing active CPAM incorporating solvent naphtha (SN) as a diluent and polymerized methylene diphenyl diisocyanate (PMDI) as a polymer modifier. Various SN-to-PMDI ratios and SN-PMDI contents relative to virgin bitumen (VB) were evaluated to produce cold patch asphalt liquid (CPAL) and the corresponding CPAMs. Viscosity tests confirmed that SN effectively reduces VB viscosity, ensuring its workability. Specifically, adding 10 % SN reduced VB viscosity by approximately 30 %, while higher SN content (e.g., 30 %) significantly compromised mechanical performance. Mechanical evaluations, including Marshall stability, moisture susceptibility, crack resistance, freeze-thaw resistance, and rutting resistance, demonstrated that CPAM containing 20 % SN-PMDI with a 50:50 SN-to-PMDI ratio achieved excellent mechanical performance comparable to hot mix asphalt (HMA). Mechanism analysis through FTIR tests further revealed that PMDI reacts with atmospheric moisture, transforming isocyanate groups (-NCO) into carbamate groups (-NHCOO), and also interacts with hydroxyl groups on limestone aggregates, forming carbamate compounds, which contribute to a 20 % increase in strength development. Overall, this study introduces a novel approach for preparing high-performance CPAM, providing a promising solution for durable and efficient pothole repairs in practical engineering applications
Betting Democracy on Epistemology
Get PDFThis paper examines two major challenges to epistemic theories of democracy: the authority dilemma and the epistemic gamble. The first is a conceptual challenge, suggesting that epistemic democracy is inherently self-undermining. The second is a normative challenge, asserting that the case for democracy should not rely on precarious epistemic grounds. I argue that both challenges fail, demonstrating that epistemic theories of democracy withstand these two prominent objections
Milk lipidome alterations in first-lactation dairy cows with lameness: A biomarker identification approach using untargeted lipidomics and machine learning
Get PDFLameness, defined as an impaired gait, impacts cow welfare and performance, compromising future health and production, and increasing culling risk. Untargeted milk lipidomics, together with the use of machine learning methods, have shown promise in identifying potential biomarkers for the early detection of lameness, before the development of visible clinical lameness. Prediction of early lameness would allow for the earlier implementation of management and treatment strategies, ultimately reducing the negative consequences. This study aimed to evaluate the predictive accuracy of differences in the milk metabolome and identify milk lipid biomarkers for early lameness detection in first-lactation dairy cows. Untargeted lipidomics and machine learning approaches were used to evaluate the differences in the milk metabolomic profiles in samples collected from heifers during the transition period (before lameness) and at the time of first lameness onset. A total of 56 milk samples from 32 cows (16 lame, 16 control) were analyzed by liquid chromatography–high-resolution mass spectrometry after calving (before lameness) and at lameness onset. Elastic net regression achieved 83% accuracy in predicting lameness from samples collected after calving and 100% accuracy at the time of lameness. A total of 10 mass ions selected by different statistical methods showed potential to be considered predictors of lameness. Pathway analysis revealed significant dysregulation of retinol metabolism after calving in cows that go on to develop lameness in that lactation. This study demonstrated potential for using milk lipidomics for early lameness detection. This, in turn, provides insights into lameness pathogenesis, furthering our understanding of lameness, with the ultimate goal of developing interventions to improve dairy cow welfare and farm productivity
The Protection of Works of Applied Art under EU Copyright Law – Opinion of the European Copyright Society in Mio/konektra (Cases C-580/23 and C-795/23)
Get PDFIn Cofemel, the Court of Justice of the European Union held that works of applied art are subject to the same originality requirement as other works (namely that the work be an expression of the author’s own intellectual creation). At the same time, the CJEU recognized the potential dangers of a generous approach when a work is recognized as an original work of applied art, in particular, the potential to undermine the specific legislative regime protecting designs. The Court indicated that copyright law should only exceptionally offer protection to designs. Two cases pending before the CJEU – Mio and konektra – both relating to claims to copyright in modernist furniture, highlight two consequences of this earlier case-law: firstly, how to apply the test in practice to ensure that copyright law is not granted too readily to designs; and, secondly, how far the test of infringement, initially elaborated in Infopaq, can also be made compatible with that goal. This Opinion of the European Copyright Society seeks to help the Court clarify when works of applied art should benefit from copyright protection and makes proposals relating to the scope of protection
Evaluation of in vitro and in vivo release of recombinant human nerve growth factor from bioengineered human stromal lenticule
Get PDFIntroduction: Small incision lenticule extraction (SMILE)-derived lenticules have been repurposed as biocompatible scaffolds to incorporate and release therapeutic substances for ocular therapeutics. We aim to investigate the in vitro and in vivo release profiles of recombinant human nerve growth factor (rhNGF) from bioengineered human stromal lenticules prepared with microparticles incorporated with rhNGF (rhNGF-MPs) for up to 1 and 4 weeks, respectively. Methods: Upon bioengineered lenticule implantation, slit lamp, Anterior Segment Optical Coherence Tomography, and In Vivo Confocal Microscopy were performed to assess corneal biocompatibility, central corneal thickness (CCT), corneal nerve -fiber density (CNFD), -branch density, and -fiber length. Rabbit cornea, tears and aqueous humour were collected to quantify rhNGF release in vivo. Results: A rapid in vitro release of rhNGF was detected until day 2, and with sustained release over 7 days. The pattern remains comparable even with the presence of antibiotic-antimycotic, trypan blue or fluorescein. Throughout the in vivo follow-up, no signs of corneal haze, edema, infiltration, or pathological increase in CCT were observed. A significant increase in CNFD (p = 0.001) at week 4 was reported in rhNGF-MPs than in Blank-MPs group. Finally, significantly higher NGF content in rabbit cornea and tear was found in rhNGF-MPs group compared to the endogenous NC group (p = 0.035 and p = 0.043, respectively). Discussion: Bioengineered lenticules exhibit sustained rhNGF release for at least 7 days in vitro and up to 1 month in vivo. These results, together with absence of adverse effects, and significant increase in CNFD at 4 weeks after lenticule implantation suggest its promising potential for clinical use
The Indo-European Cognate Relationships dataset
Get PDFThe Indo-European Cognate Relationships (IE-CoR) dataset is an open-access relational dataset showing how related, inherited words (‘cognates’) pattern across 160 languages of the Indo-European family. IE-CoR is intended as a benchmark dataset for computational research into the evolution of the Indo-European languages. It is structured around 170 reference meanings in core lexicon, and contains 25731 lexeme entries, analysed into 4981 cognate sets. Novel, dedicated structures are used to code all known cases of horizontal transfer. All 13 main documented clades of Indo-European, and their main subclades, are well represented. Time calibration data for each language are also included, as are relevant geographical and social metadata. Data collection was performed by an expert consortium of 89 linguists drawing on 355 cited sources. The dataset is extendable to further languages and meanings and follows the Cross-Linguistic Data Format (CLDF) protocols for linguistic data. It is designed to be interoperable with other cross-linguistic datasets and catalogues, and provides a reference framework for similar initiatives for other language families
Availability Assessment of Offshore Wind Turbines with Condition-based Opportunistic Maintenance Using GSPN
Get PDFThis paper assesses the availability of an offshore wind turbine under condition-based opportunistic maintenance strategies. Generalized stochastic Petri nets (GSPN) are adopted to analyze the impact of implementing the maintenance strategy, with the consideration of factors such as vessel hiring and weather windows. A 25-year operational period is simulated using a Monte-Carlo simulation to evaluate availability and total cost of the wind turbine. By examining the availability and total cost under various opportunistic maintenance efficiencies, it is concluded that an opportunistic maintenance efficiency in a certain range offers a cost-availability trade-off. Overall, the method and the results of this paper contribute to the effective operation and maintenance of offshore wind turbines
Living with mental health issues: citizen science project on self-management strategies
Get PDFPeople living with mental health issues use a range of self-management strategies. Most strategy recommendations have been developed by clinicians and researchers, so they may not reflect the full range of approaches used in practice. A citizen mental health science methodology can address this bias in strategy identification. We co-created a list of 77 pre-defined self-management strategies, and 1116 public contributors (n = 468 mental health service users, n = 497 lived experience not using services, n = 151 no lived experience) living in the United Kingdom completed an online survey identifying their use of each strategy, and identifying extra strategies. A wide range of pre-defined strategies were used by contributors, with differences in usage patterns identified between the three groups. 401 distinct extra strategies were identified. The active use of avoidance as a self-management strategy was more common than anticipated, including avoiding alcohol, social media, thinking about problems, other people, and mental health services
Navigating NHS commissioning for digital mental health: a perspective on learning through collaboration
No full textDigital mental health interventions (DMHIs) offer promising solutions to address unmet mental health needs among children and young people, yet how to get DMHIs commissioned into the NHS can seem mystifying for innovators. This perspective paper draws on insights from a collaborative commissioning event focused on the Online Remote Behavioural Intervention for Tics (ORBIT) intervention, a digital behavioural therapy for young people with tic disorders, to explore the barriers and enablers to commissioning DMHIs in England. Key challenges identified include unclear commissioning pathways, limited clinical expertise, integration hurdles, and short-term funding models. Enablers included clinical advocacy, robust research evidence, and alignment with national frameworks. These insights highlight the importance of early collaboration between academics, developers, and policymakers in the product development cycle seeking to bridge the gap between innovation and implementation in digital mental health care
Interplay of host and viral genetic variations in modulating antibody responses to genotype 3a hepatitis C virus: Implications for vaccine design
Get PDFHepatitis C virus (HCV) exhibits significant genetic diversity and is a cause of severe liver complications. The viral envelope glycoproteins E1 and E2, key targets for neutralizing antibodies, are highly variable. To understand how host and viral genetic factors modulate antibody responses, we analyze genetic and antibody binding and neutralization data from 54 patients infected with HCV genotype 3a. We find that host polymorphisms in IFNL4 gene (IFNλ4-P70 generating haplotype) are associated with reduced antibody binding. Within the virus, variations at three specific E1/E2 amino acid positions and three N-glycosylation sites (including one site common to both analyses) significantly correlate with antibody binding and/or neutralization sensitivity. Furthermore, greater intra-patient diversity within the E2 hypervariable region 1 is associated with stronger antibody binding. These results identify specific host and viral genetic features that shape humoral immunity against HCV genotype 3a, providing insights crucial for designing broadly effective vaccines
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